Nrf2 is involved in the expression of various antioxidant proteins (such as detoxifying enzymes) via antioxidant response element binding site, hyperglycemia leads to oxidative stress and results in changes in levels of Nrf2, persistent hyperglycemia decreases its expression of Nrf2, and evidence has also indicated decreased levels of Nrf2 in diabetes (51). This evidence concerns the gene NFE2L2 and diabetes mellitus.